Title:The Role of P2X Receptors in Bone Biology
Volume: 22
Issue: 7
Author(s): N.R. Jørgensen, S. Syberg and M. Ellegaard
Affiliation:
Keywords:
Bone biology, bone formation, bone resorption, bone turnover, P2X receptor, osteoblast, osteoclast, osteocyte, osteoporosis,
single nucleotide polymorphism.
Abstract: Bone is a highly dynamic organ, being constantly modeled and remodeled in order to adapt to
the changing need throughout life. Bone turnover involves the coordinated actions of bone formation and
bone degradation. Over the past decade great effort has been put into the examination of how P2X receptors
regulate bone metabolism and especially for the P2X7 receptor an impressive amount of evidence has now documented
its expression in osteoblasts, osteoclasts, and osteocytes as well as important functional roles in proliferation, differentiation,
and function of the cells of bone. Key evidence has come from studies on murine knockout models and from
pharmacologic studies on cells and animals. More recently, the role of P2X receptors in human bone diseases has been
documented. Loss-of-functions polymorphisms in the P2X7 receptorare associated with bone loss and increased fracture
risk. Very recently a report from a genetic study in multiple myeloma demonstrated that decreased P2X7 receptor function
was associated with increased risk of developing multiple myeloma. In contrast, the risk of developing myeloma bone disease
and subsequent vertebral fractures was increased in subjects carrying P2X7 receptor gain-of-function alleles as compared
to subjects only carrying loss-of-function or normal functioning alleles. It is evident that P2X receptors are important
in regulating bone turnover and maintaining bone mass, and thereby holding great potential as novel drug targets for
treatment of bone diseases. However, further research is needed before we fully understand the roles and effects of P2X
receptors in bone.
